Quetiapine,2-(2-(4-dibenzo[b,f][1,4]thiazepin-11-yl-1-piperazinyl)ethoxy)ethanol, having the following chemical structure:
is a psychoactive organic compound that acts as an antagonist for multiple neurotransmitter receptors in the brain and acts as an antipsychotic agent reportedly useful for treating, among other things, schizophrenia. Merck Index, 13th Ed., 8130 (2001). This drug, having the CAS number: 111974-69-7, was approved under the trademark Seroquel®, by the U.S. Food and Drug Administration and is available from the innovator, AstraZeneca PLC. Quetiapine can be made, for example, as taught in the U.S. Pat. No. 4,879,288, incorporated in its entirety herein by reference.
As taught in the '288 patent, quetiapine can be made via reaction of formula I, 11-piperazinyl dibenzo[b,f]-[1,4]thiazepine hydrochloride and about a 2 molar equivalent of formula II, 1-(2-hydroxyethoxyethyl)piperazine,
wherein the reaction time is about 30 hours, the yield is about 77%, and puritfication is by flash chromotpgraphy.
Thus, there is a need in the art for an improved process for making quetiapine and salts thereof from 11-piperazinyl dibenzo[b,f]-[1,4]thiazepine and 2-(2-chloroethoxy)ethanol using less than a 2 molar equivalent of 2-(2-chloroethoxy)ethanol with respect to 11-piperazinyl dibenzo[b,f]-[1,4]thiazepine, a shorter reaction time, and affording a quetiapine product that contains a lower level of impurities (such as the unreacted starting material) so that the process can be easily, conveniently, and inexpensively applied on an industrial scale.